Download COMPARATIVE HEPATOPROTECTIVE ACTIVITY OF LIV-52 AND SILYMARINE AGAINST

Academic Sciences
International Journal of Pharmacy and Pharmaceutical Sciences
ISSN- 0975-1491
Vol 4, Suppl 3, 2012
Research Article
COMPARATIVE HEPATOPROTECTIVE ACTIVITY OF LIV-52 AND SILYMARINE AGAINST
HEPATOTOXICITY INDUCED BY ANTIANDROGEN –BICALUTAMIDE IN RATS
V.B. FULZELE*, A.T. SHEDAGE, A. ANTON SMITH, T.V. GAIKWAD, S.R. KIRTANE
Department of Pharmacy, Annamalai University, Annamalai Nagar, Chidambaram, Tamil Nadu 608002, India.
* Email: [email protected]
Received: 29 Dec 2011, Revised and Accepted: 15 Mar 2012
ABSTRACT
Bicalutamide is a nonsteroidal antiandrogenic drug used in treatment of prostate cancer. Bicalutamide is extensively metabolized by liver and
reported to have hepatotoxicity. The present study was conducted to compare the hepatoprotective activity of two formulations, Liv-52 and
Silymarine against Bicaluatmide induced hepatotoxicity. The serum enzyme level of Glutamate Pyruvate Transaminase (SGPT), Glutamate
Oxaloacetate Transaminase (SGOT) and histopathological examination of liver was done after treating the animals for fourteen days. The animals
treated with Liv-52 shows a significant decrease in SGPT level and no significant changes in histology of liver. It was concluded from study that Liv52 has more significant hepatoprotective activity against Bicalutamide in rats in comparison to Silymarine.
Keywords: Bicalutamide, Hepatoprotective, Liv -52, Silymarine, SGPT, SGOT.
INTRODUCTION
Liver play a major role in detoxification and excretion of many
endogenous and exogenous compounds. Any type of injury (due to
systemic drug, food preservatives, agrochemicals and addiction to
alcohol) or impairment of its function may lead to many
complications in one’s health. There is a no rational therapy
available for liver disorders and it is a still challenge to modern
medicine1. Hepatic injury can be life threatening when the entirely
or most of the liver is exposed to any hepatotoxin, including
Bicalutamide2.
Bicalutamide is a nonsteroidal antiandrogenic drug used in
treatment of prostate cancer3. The most common adverse effects of
Bicalutamide are induced by its pharmacological properties of
competitive androgen receptor blockade include gynacomastia, hot
flashes, fatigue and decreased libido, increased liver function test are
seen with Bicalutamide therapy. Regular liver function test are
advised during treatment of prostate cancer by anti androgen like
Bicalutamide 4, 5.
Present study was conducted to compare the hepatoprotective
activity of two marketed formulations Liv-52 and Silymarine against
Bicalutamide induced hepatotoxicity in rats.
MATERIALS AND METHODS
Animal
Wister strain male rat having a weight range of 150-180 gm were
used for the experiment.
The animals were well housed in polypropylene cage under hygiene
condition and maintained at 28 ± 2oC temp. The animals were
allowed to have food and water adding ad libitum. The animal
institutional ethical committee approved the experimental protocol.
(Proposal no.416/160/1999/CPCSEA)
Chemicals and drugs
Liv-52 syrup (Himalaya drug company) and Silymarine (Silybon,
Micro Labs Limited) were used for hepatoprotective activity and
Bicalutamine (Cipla Pharmaceuticals Pvt. Limited) was used to
induce hepatotoxicity.
Experimental design
Animals were divided into four groups (n= 6)
Group I (N): Control vehicle i.e. distilled water
Group II (B): Bicalutamide 25mg/kg/day p.o6
Group III (BL): Bicalutamide
2ml/100gm/day p.o7
GroupIV (BS): Bicalutamide
50mg/kg/day p.o,8 9.
25mg/kg/day
25mg/kg/day
The entire animals were treated for 14 days.
and
and
Liv
52
Silymarine
Biochemical estimation
The blood samples were collected on 0th day and on 15th day (24 hrs
after last dose) for biochemical study. The blood was obtained from
all the animals by puncturing the retro-orbital plexus. The blood
samples were allowed to clot for 30 minutes at room temperature.
Serum was separated by centrifugation at 2500 rpm for 15 minutes
at 300C and utilized for estimation of various biochemical
parameters mainly SGOT and SGPT10, 11, 12.
Histopathological examination
All the animals were sacrificed on 15th day and livers were removed,
washed with saline. The liver pieces were preserved in 10 %
formalin solution for histopathological study. The sections were
approximately 4-6 micron in thickness. They were stained with
hematoxylene and eosin and photographed 13, 14.
Statistical Analysis
The data were expressed as mean ± SD; for obtaining this data
biochemical and physiological parameters were statistically
analyzed using one way ANOVA followed Dunnet test. For
comparison with the control group and Bicalutamide treated group,
P< 0.05 set at the minimum level of significance.
Table 1: Effect of Liv-52 and Silymarine on Bicalutamide
induced hepatotoxicity
Group I
Group II
Group III
Group IV
SGOT(IU/L)
21.26±1.163
28.51±0.4600
24.8±1.550*
20.29±0.6981
SGPT (IU/L)
46.40±0.4177
49.33 ±2.719
47.317±1.531
48.717±2.057
Group Biochemical parameters mean ±SEM; *Significant (p <0.05)
reduction compare to Bicalutamide
Histopathology of liver
Liver sections of 4-6 micron in thickness were stained with
hematoxylin and eosin and observed under H & E x100 resolution of
microscope for histopathological changes and photographed.
Fulzele et al.
Int J Pharm Pharm Sci, Vol 4, Suppl 3, 211-213
SGOT
SGPT
54
35
30
25
20
15
10
5
0
MEAN &SEM
MEAN & SEM
52
50
48
46
44
42
N
B
BL
BS
GROUPS
N
B
BL
BS
GROUPS
Fig. 1: Control group: No specific change.
Fig. 2: Bicalutamide-lymphocyte sinusoidal inflammation, Kupffer
cell hyperplasic, congested- dilated blood vessels, non necrosis
fibrosis.
Fig. 3: Bicalutamide with LIV52- Non-specific changes.
Fig.4: Biclutamide with Silymarin- Focal lymphocyte, Kupffer cell
hyperplasic, some congested- dilated blood vessels.
RESULTS AND DISCUSSION
The results of Bicalutamide induced hepatotoxicity are shown in
table 1. Bicalutamide intoxication in normal rat significantly
elevated the serum levels of SGOT and SGPT. The rats treated with
Liv-52 and Silymarine showed reduction in all biochemical
parameters.
In histopathological examination of liver sections of control group,
(Fig. 1) no specific change was obverse. In the Bicalutamide
intoxicated group (Fig. 2), lymphocyte sinusoidal inflammation,
Kupffer cell hyperplasic, congested- dilated blood vessels non
necrosis fibrosis. In the histopathological profile of Liv-52 treated
group (Fig.3), no specific change. In the histopathological profile of
Silymarine (Fig. 4), Focal lymphocyte, Kupffer cell hyperplasic, some
congested- dilated blood vessels15, 16, 17.
Liv-52 formulation was able to control this necrotic change that was
comparable to that of Silymarine. Thus biochemical observation corelates well with the histopathology results of the liver samples.
These above observations confirmed that the potent
hepatoprotective activity of liv52 than that of Silymarine.
In this study rats treated with a repeated dose of Bicalutamide to
develop hepatic damage which was observed from a substantial
increase in the activity of serum like SGOT and SGPT.
Histipathological study is indicative of cellular leakage and loss of
the functional integrity of cell membrane in liver.
212
Fulzele et al.
CONCLUSION
Overall, the result of the present study indicates that Liv-52
demonstrate a significant hepatoprotective activity against
Bicalutamide induced hepatotoxicity in rats than silymarin.
ACKNOWLEDGMENT
The authors are thankful to Prof. (Dr.) Madhavan Nirmal,
Department of Oral Pathology and Microbiology, Faculty of
Dentistry, RMMCH, Annamalai University, Chidambaram, and Prof.
(Dr.) Kotheesaravam, Mahatma Gandhi medical college Pondicherry,
whose support is significant for the work.
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